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Recombinant GPI-anchored TIMP-1 stimulates growth and migration of peritoneal mesothelial cells.
PLoS ONE 7:e33963 (2012)
Background: Mesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity. Methods and Finding: By modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-alpha and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-beta 1. Conclusions: TIMP-1-GPI stimulated rapid and efficient in vitro wound closure. The agent enhanced mesothelial cell proliferation and migration and was bioactive in the nanogram range. The application of TIMP-1-GPI may represent a new approach for limiting or repairing damaged mesothelium.
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4.092
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
MATRIX METALLOPROTEINASES; FIBRINOLYTIC SYSTEM; TISSUE INHIBITORS; CAPD PATIENTS; GELATINASE-B; TGF-BETA; EXPRESSION; APOPTOSIS; CYTOKINES; ANGIOGENESIS
Language
english
Publication Year
2012
HGF-reported in Year
2012
ISSN (print) / ISBN
1932-6203
Journal
PLoS ONE
Quellenangaben
Volume: 7,
Issue: 4,
Article Number: e33963
Publisher
Public Library of Science (PLoS)
Publishing Place
Lawrence, Kan.
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501700-001
PubMed ID
22558080
WOS ID
WOS:000305336000008
Scopus ID
84860441448
Erfassungsdatum
2012-07-12